U.S. patent application number 11/897103 was filed with the patent office on 2008-03-06 for system and method for augmenting a humoral immune response.
This patent application is currently assigned to Searete LLC. Invention is credited to Muriel Y. Ishikawa, Edward K.Y. Jung, Nathan P. Myhrvold, Richa Wilson, Lowell L. JR. Wood.
Application Number | 20080059136 11/897103 |
Document ID | / |
Family ID | 36575464 |
Filed Date | 2008-03-06 |
United States Patent
Application |
20080059136 |
Kind Code |
A1 |
Ishikawa; Muriel Y. ; et
al. |
March 6, 2008 |
System and method for augmenting a humoral immune response
Abstract
The present application relates, in general, to a system and/or
method for detection and/or treatment.
Inventors: |
Ishikawa; Muriel Y.;
(Livermore, CA) ; Jung; Edward K.Y.; (Bellevue,
WA) ; Myhrvold; Nathan P.; (Medina, WA) ;
Wilson; Richa; (San Francisco, CA) ; Wood; Lowell L.
JR.; (Livermore, WA) |
Correspondence
Address: |
SEARETE LLC;CLARENCE T. TEGREENE
1756 - 114TH AVE., S.E.
SUITE 110
BELLEVUE
WA
98004
US
|
Assignee: |
Searete LLC
Bellevue
WA
|
Family ID: |
36575464 |
Appl. No.: |
11/897103 |
Filed: |
August 28, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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11004446 |
Dec 3, 2004 |
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11897103 |
Aug 28, 2007 |
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Current U.S.
Class: |
703/11 |
Current CPC
Class: |
A61K 31/55 20130101;
Y02A 50/30 20180101; A61K 39/02 20130101; A61K 39/00 20130101; Y02A
50/403 20180101 |
Class at
Publication: |
703/011 |
International
Class: |
G06G 7/60 20060101
G06G007/60 |
Claims
1.-53. (canceled)
54. A system, comprising: circuitry for associating at least one
computable antigen of one or more agents with at least a part of an
immune response; circuitry for projecting a pattern of one or more
changes relating to the at least one computable antigen of the one
or more agents; and circuitry for selecting one or more immune
response components responsive to said circuitry for
projecting.
55. (canceled)
56. A system, comprising: circuitry for accepting an input of one
or more agents; and circuitry for identifying an association of at
least one computable antigen of one or more agents with at least a
part of an immune response related to suppressing the one or more
agents.
57. (canceled)
58. A system, comprising: circuitry for projecting a pattern of one
or more changes relating to at least one computable antigen of one
or more agents; and circuitry for selecting one or more immune
response components in response to said projecting.
59. (canceled)
60. (canceled)
61. The system of claim 54, wherein the circuitry for associating
at least one computable antigen of one or more agents with at least
a part of an immune response comprises: circuitry for identifying
an association of at least one computable antigen with one or more
agents wherein at least one of the one or more agents is a putative
causative agent of a disease.
62. The system of claim 54, wherein the circuitry for associating
of at least one computable antigen of one or more agents with at
least a part of an immune response comprises: circuitry for
identifying an association of at least one computable antigen with
one or more agents wherein at least one of the one or more agents
is an agent belonging to the same family or group as the agent of
primary interest.
63. The system of claim 54, wherein the circuitry for associating
of at least one computable antigen of one or more agents with at
least a part of an immune response comprises: circuitry for
identifying an association of at least one computable antigen with
one or more agents wherein at least one of the one or more agents
is an agent exhibiting a common function relative to the agent of
primary interest.
64. (canceled)
65. (canceled)
66. The system of claim 54, wherein the circuitry for selecting one
or more immune response components responsive to said circuitry for
projecting comprises: circuitry for selecting at least a part of at
least one B-lymphocyte.
67. The system of claim 54, wherein the circuitry for selecting one
or more immune response components responsive to said circuitry for
projecting comprises: circuitry for selecting one or more
modulators of at least a part of a B-lymphocyte.
68. (canceled)
69. (canceled)
70. The system of claim 54, wherein the circuitry for selecting one
or more immune response components responsive to said circuitry for
projecting comprises: circuitry for selecting one or more immune
response components specific to the conformational state of a
protein.
71. The system of claim 54, wherein the circuitry for selecting one
or more immune response components responsive to said circuitry for
projecting comprises: circuitry for selecting one or more immune
response components including one or more effector molecules.
72. The system of claim 54, wherein the circuitry for selecting one
or more immune response components responsive to said circuitry for
projecting comprises: circuitry for selecting one or more immune
response components with physico-chemical properties optimized by
computer-based screening methods.
73. The system of claim 54, wherein the circuitry for selecting one
or more immune response components responsive to said circuitry for
projecting comprises: circuitry for selecting one or more immune
response components designed to include accommodations in its
design arising from the prediction of mutational changes in an
epitope.
74. The system of claim 54, wherein the circuitry for selecting one
or more immune response components responsive to said circuitry for
projecting comprises: circuitry for selecting one or more immune
response components designed for binding to the smallest effective
determinant.
75. The system of claim 56, wherein the circuitry for accepting an
input of one or more agents comprises: circuitry for accepting
input via a medical system.
76. The system of claim 56, wherein the circuitry for accepting an
input of one or more agents comprises: circuitry for accepting
input including criteria related to the agent.
77. (canceled)
78. The system of claim 56, wherein the circuitry for identifying
an association of at least one computable antigen of one or more
agents with at least a part of an immune response comprises:
circuitry for identifying an association of at least one computable
antigen with one or more agents wherein at least one of the one or
more agents is a putative causative agent of a disease.
79. The system of claim 56, wherein the circuitry for identifying
an association of at least one computable antigen of one or more
agents with at least a part of an immune response comprises:
circuitry for identifying an association of at least one computable
antigen with one or more agents wherein at least one of the one or
more agents is an agent belonging to the same family or group as
the agent of primary interest.
80. The system of claim 56, wherein the circuitry for identifying
an association of at least one computable antigen of one or more
agents with at least a part of an immune response comprises:
circuitry for identifying an association of at least one computable
antigen with one or more agents wherein at least one of the one or
more agents is an agent exhibiting a common function relative to
the agent of primary interest.
81. (canceled)
82. (canceled)
83. The system of claim 58, wherein the circuitry for selecting one
or more immune response components in response to the projecting
comprises: circuitry for selecting at least a part of at least one
B-lymphocyte.
84. The system of claim 58, wherein the circuitry for selecting one
or more immune response components in response to the projecting
comprises: circuitry for selecting one or more modulators of at
least a part of a B-lymphocyte.
85. (canceled)
86. (canceled)
87. The system of claim 58, wherein the circuitry for selecting one
or more immune response components in response to the projecting
comprises: circuitry for selecting one or more immune response
components specific to the conformational state of a protein.
88. The system of claim 58, wherein the circuitry for selecting one
or more immune response components in response to the projecting
comprises: circuitry for selecting one or more immune response
components including one or more effector molecules.
89. The system of claim 58, wherein the circuitry for selecting one
or more immune response components in response to the projecting
comprises: circuitry for selecting one or more immune response
components with physico-chemical properties optimized by
computer-based screening methods.
90. The system of claim 58, wherein the circuitry for selecting one
or more immune response components in response to the projecting
comprises: circuitry for selecting one or more immune response
components designed to include accommodations in its design arising
from the prediction of mutational changes in an epitope.
91. The system of claim 58, wherein the circuitry for selecting one
or more immune response components in response to the projecting
comprises: circuitry for selecting one or more immune response
components designed for binding to the smallest effective
determinant.
Description
CROSS-REFERENCE TO RELATED-APPLICATIONS
[0001] The present application is related to, claims the earliest
available effective filing date(s) from (e.g., claims earliest
available priority dates for other than provisional patent
applications; claims benefits under 35 USC .sctn.119(e) for
provisional patent applications), and incorporates by reference in
its entirety all subject matter of the following listed
application(s) (the "Related Applications"); the present
application also claims the earliest available effective filing
date(s) from, and also incorporates by reference in its entirety
all subject matter of any and all parent, grandparent,
great-grandparent, etc. applications of the Related Application(s).
The United States Patent Office (USPTO) has published a notice to
the effect that the USPTO's computer programs require that patent
applicants reference both a serial number and indicate whether an
application is a continuation or continuation in part. The present
applicant entity has provided below a specific reference to the
application(s)from which priority is being claimed as recited by
statute. Applicant entity understands that the statute is
unambiguous in its specific reference language and does not require
either a serial number or any characterization such as
"continuation" or "continuation-in-part." Notwithstanding the
foregoing, applicant entity understands that the USPTO's computer
programs have certain data entry requirements, and hence applicant
entity is designating the present application as a continuation in
part of its parent applications, but expressly points out that such
designations are not to be construed in any way as any type of
commentary and/or admission as to whether or not the present
application contains any new matter in addition to the matter of
its parent application(s).
Related Applications:
[0002] 1. For purposes of the USPTO extra-statutory requirements,
the present application constitutes a continuation in part of
currently co-pending United States patent application entitled A
SYSTEM AND METHOD RELATED TO IMPROVING AN IMMUNE SYSTEM naming
Muriel Y. Ishikawa, Edward K. Y. Jung, Nathan P. Myhrvold, Richa
Wilson, and Lowell L. Wood, Jr. as inventors, filed 24 Aug. 2004
having U.S. application Ser. No. 10/925,904. [0003] 2. For purposes
of the USPTO extra-statutory requirements, the present application
constitutes a continuation in part of currently co-pending United
States patent application entitled A SYSTEM AND METHOD FOR
HEIGHTENING AN IMMUNE RESPONSE naming Muriel Y. Ishikawa, Edward K.
Y. Jung, Nathan P. Myhrvold, Richa Wilson, and Lowell L. Wood, Jr.
as inventors, filed 25 Aug., 2004 having U.S. application Ser. No.
10/926,753. [0004] 3. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a continuation in
part of currently co-pending United States patent application
entitled A SYSTEM AND METHOD RELATED TO AUGMENTING AN IMMUNE SYSTEM
naming Muriel Y. Ishikawa, Edward K. Y. Jung, Nathan P. Myhrvold,
Richa Wilson, and Lowell L. Wood, Jr. as inventors, filed 24 Aug.,
2004 having U.S. application Ser. No. 10/925,905. [0005] 4. For
purposes of the USPTO extra-statutory requirements, the present
application constitutes a continuation in part of currently
co-pending United States patent application entitled A SYSTEM AND
METHOD RELATED TO ENHANCING AN IMMUNE SYSTEM naming Muriel Y.
Ishikawa, Edward K. Y. Jung, Nathan P. Myhrvold, Richa Wilson, and
Lowell L. Wood, Jr. as inventors, filed 24 Aug., 2004 having U.S.
application Ser. No. 10/925,902. [0006] 5. For purposes of the
USPTO extra-statutory requirements, the present application
constitutes a continuation in part of currently co-pending United
States patent application entitled A SYSTEM AND METHOD FOR
MAGNIFYING AN IMMUNE RESPONSE naming Muriel Y. Ishikawa, Edward K.
Y. Jung, Nathan P. Myhrvold, Richa Wilson, and Lowell L. Wood, Jr.
as inventors, filed 25 Aug., 2004 having U.S. application Ser. No.
10/926,881. [0007] 6. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a continuation in
part of currently co-pending United States patent application
entitled A SYSTEM AND METHOD FOR MODULATING A HUMORAL IMMUNE
RESPONSE naming Muriel Y. Ishikawa, Edward K. Y. Jung, Nathan P.
Myhrvold, Richa Wilson, and Lowell L. Wood, Jr. as inventors, filed
1 Dec., 2003 having a U.S. application Ser. No. of [to be
assigned]. [0008] 7. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a continuation in
part of currently co-pending United States patent application
entitled A SYSTEM AND METHOD FOR HEIGTENING A HUMORAL IMMUNE
RESPONSE naming Muriel Y. Ishikawa, Edward K. Y. Jung, Nathan P.
Myhrvold, Richa Wilson, and Lowell L. Wood, Jr. as inventors, filed
contemporaneously herewith.
TECHNICAL FIELD
[0009] The present application relates, in general, to detection
and/or treatment.
SUMMARY
[0010] In one aspect, a method includes but is not limited to:
identifying an association of at least a computable portion of one
or more agents with at least a part of an immune response;
projecting a pattern of one or more changes relating to the at
least a computable portion of the one or more agents; and selecting
one or more immune response components in response to the
projecting. In addition to the foregoing, other method aspects are
described in the claims, drawings, and text forming a part of the
present application.
[0011] In one aspect, a system includes but is not limited to:
circuitry for identifying an association of at least a computable
portion of one or more agents with at least a part of an immune
response; circuitry for projecting a pattern of one or more changes
relating to the at least a computable portion of the one or more
agents; and circuitry for selecting one or more immune response
components responsive to said circuitry for projecting. In addition
to the foregoing, other system aspects are described in the claims,
drawings, and text forming a part of the present application.
[0012] In one aspect, a method includes but is not limited to:
accepting an input of one or more agents; and identifying an
association of at least a computable portion of one or more agents
with at least a part of an immune response related to suppressing
the one or more agents. In addition to the foregoing, other method
aspects are described in the claims, drawings, and text forming a
part of the present application.
[0013] In one aspect, a system includes but is not limited to:
circuitry for accepting an input of one or more agents; and
circuitry for identifying an association of at least a computable
portion of one or more agents with at least a part of an immune
response related to suppressing the one or more agents. In addition
to the foregoing, other system aspects are described in the claims,
drawings, and text forming a part of the present application.
[0014] In one aspect, a method includes but is not limited to:
projecting a pattern of one or more changes relating to at least a
computable portion of one or more agents; and selecting one or more
immune response components in response to said projecting. In
addition to the foregoing, other method aspects are described in
the claims, drawings, and text forming a part of the present
application.
[0015] In one aspect, a system includes but is not limited to:
circuitry for projecting a pattern of one or more changes relating
to at least a computable portion of one or more agents; and
circuitry for selecting one or more immune response components in
response to said projecting. In addition to the foregoing, other
system aspects are described in the claims, drawings, and text
forming a part of the present application.
[0016] In one aspect, a method includes but is not limited to:
identifying an association of at least one computable epitope of
one or more agents with at least a part of an immune response;
projecting a pattern of one or more changes relating to the at
least one computable epitope of the one or more agents; and
selecting one or more immune response components in response to the
projecting In addition to the foregoing, other method aspects are
described in the claims, drawings, and text forming a part of the
present application.
[0017] In one aspect, a system includes but is not limited to:
circuitry for identifying an association of at least one computable
epitope of one or more agents with at least a part of an immune
response; circuitry for projecting a pattern of one or more changes
relating to the at least one computable epitope of the one or more
agents; and circuitry for selecting one or more immune response
components responsive to said circuitry for projecting. In addition
to the foregoing, other system aspects are described in the claims,
drawings, and text forming a part of the present application.
[0018] In one aspect, a method includes but is not limited to:
accepting an input of one or more agents; and identifying an
association of at least one computable epitope of one or more
agents with at least a part of an immune response related to
suppressing the one or more agents. In addition to the foregoing,
other method aspects are described in the claims, drawings, and
text forming a part of the present application.
[0019] In one aspect, a system includes but is not limited to:
circuitry for accepting an input of one or more agents; and
circuitry for identifying an association of at least one computable
epitope of one or more agents with at least a part of an immune
response related to suppressing the one or more agents. In addition
to the foregoing, other system aspects are described in the claims,
drawings, and text forming a part of the present application.
[0020] In one aspect, a method includes but is not limited to:
projecting a pattern of one or more changes relating to at least
one computable epitope of one or more agents; and selecting one or
more immune response components in response to said projecting. In
addition to the foregoing, other method aspects are described in
the claims, drawings, and text forming a part of the present
application.
[0021] In one aspect, a system includes but is not limited to:
circuitry for projecting a pattern of one or more changes relating
to at least one computable epitope of one or more agents; and
circuitry for selecting one or more immune response components in
response to said projecting. In addition to the foregoing, other
system aspects are described in the claims, drawings, and text
forming a part of the present application.
[0022] In one aspect, a method includes but is not limited to:
identifying an association of at least one antigen of one or more
agents with at least a part of an immune response; projecting a
pattern of one or more changes relating to at least one antigen of
the one or more agents; and selecting one or more immune response
components in response to said projecting. In addition to the
foregoing, other method aspects are described in the claims,
drawings, and text forming a part of the present application.
[0023] In one aspect, a system includes but is not limited to:
circuitry for identifying an association of at least one antigen of
one or more agents with at least a part of an immune response;
circuitry for projecting a pattern of one or more changes relating
to the at least one antigen of the one or more agents; and
circuitry for selecting one or more immune response components
responsive to said circuitry for projecting. In addition to the
foregoing, other system aspects are described in the claims,
drawings, and text forming a part of the present application.
[0024] In one aspect, a method includes but is not limited to:
accepting an input of one or more agents; and identifying an
association of at least one antigen of one or more agents with at
least a part of an immune response related to suppressing the one
or more agents. In addition to the foregoing, other method aspects
are described in the claims, drawings, and text forming a part of
the present application.
[0025] In one aspect, a system includes but is not limited to:
circuitry for accepting an input of one or more agents; and
circuitry for identifying an association of at least one antigen of
one or more agents with at least a part of an immune response
related to suppressing the one or more agents. In addition to the
foregoing, other system aspects are described in the claims,
drawings, and text forming a part of the present application.
[0026] In one aspect, a method includes but is not limited to:
projecting a pattern of one or more changes relating to at least
one antigen of one or more agents; and selecting one or more immune
response components in response to said projecting. In addition to
the foregoing, other method aspects are described in the claims,
drawings, and text forming a part of the present application.
[0027] In one aspect, a system includes but is not limited to:
circuitry for projecting a pattern of one or more changes relating
to at least one antigen of one or more agents; and circuitry for
selecting one or more immune response components in response to
said projecting. In addition to the foregoing, other system aspects
are described in the claims, drawings, and text forming a part of
the present application.
[0028] In one aspect, a method includes but is not limited to:
identifying an association of at least one epitope of one or more
agents with at least a part of an immune response; projecting a
pattern of one or more changes relating to the at least one epitope
of the one or more agents; and selecting one or more immune
response components in response to said projecting. In addition to
the foregoing, other method aspects are described in the claims,
drawings, and text forming a part of the present application.
[0029] In one aspect, a system includes but is not limited to:
circuitry for associating at least one epitope of one or more
agents with at least a part of an immune response; circuitry for
projecting a pattern of one or more changes relating to the at
least one epitope of the one or more agents; and circuitry for
selecting one or more immune response components responsive to said
circuitry for projecting. In addition to the foregoing, other
system aspects are described in the claims, drawings, and text
forming a part of the present application.
[0030] In one aspect, a method includes but is not limited to:
accepting an input of one or more agents; and identifying an
association of at least one epitope of one or more agents with at
least a part of an immune response related to suppressing the one
or more agents. In addition to the foregoing, other method aspects
are described in the claims, drawings, and text forming a part of
the present application.
[0031] In one aspect, a system includes but is not limited to:
circuitry for accepting an input of one or more agents; and
circuitry identifying an association of at least one epitope of one
or more agents with at least a part of an immune response related
to suppressing the one or more agents. In addition to the
foregoing, other system aspects are described in the claims,
drawings, and text forming a part of the present application.
[0032] In one aspect, a method includes but is not limited to:
projecting a pattern of one or more changes relating to at least
one epitope of one or more agents; and selecting one or more immune
response components in response to said projecting. In addition to
the foregoing, other method aspects are described in the claims,
drawings, and text forming a part of the present application.
[0033] In one aspect, a system includes but is not limited to:
circuitry for projecting a pattern of one or more changes relating
to at least one epitope of one or more agents; and circuitry for
selecting one or more immune response components in response to
said projecting. In addition to the foregoing, other system aspects
are described in the claims, drawings, and text forming a part of
the present application.
[0034] In one aspect, a method includes but is not limited to:
identifying an association of at least one computable antigen of
one or more agents with at least a part of an immune response;
projecting a pattern of one or more changes relating to the at
least one computable antigen of the one or more agents; and
selecting one or more immune response components in response to
said projecting. In addition to the foregoing, other method aspects
are described in the claims, drawings, and text forming a part of
the present application.
[0035] In one aspect, a system includes but is not limited to:
circuitry for associating at least one computable antigen of one or
more agents with at least a part of an immune response; circuitry
for projecting a pattern of one or more changes relating to the at
least one computable antigen of the one or more agents; and
circuitry for selecting one or more immune response components
responsive to said circuitry for projecting. In addition to the
foregoing, other system aspects are described in the claims,
drawings, and text forming a part of the present application.
[0036] In one aspect, a method includes but is not limited to:
accepting an input of one or more agents; and identifying an
association of at least one computable antigen of one or more
agents with at least a part of an immune response related to
suppressing the one or more agents. In addition to the foregoing,
other method aspects are described in the claims, drawings, and
text forming a part of the present application.
[0037] In one aspect, a system includes but is not limited to:
circuitry for accepting an input of one or more agents; and
circuitry identifying an association of at least one computable
antigen of one or more agents with at least a part of an immune
response related to suppressing the one or more agents. In addition
to the foregoing, other system aspects are described in the claims,
drawings, and text forming a part of the present application.
[0038] In one aspect, a method includes but is not limited to:
projecting a pattern of one or more changes relating to the at
least one computable antigen of one or more agents; and selecting
one or more immune response components in response to said
projecting. In addition to the foregoing, other method aspects are
described in the claims, drawings, and text forming a part of the
present application.
[0039] In one aspect, a system includes but is not limited to:
circuitry for projecting a pattern of one or more changes relating
to at least one computable antigen of one or more agents; and
circuitry for selecting one or more immune response components in
response to said projecting. In addition to the foregoing, other
system aspects are described in the claims, drawings, and text
forming a part of the present application.
[0040] The foregoing is a summary and thus contains, by necessity,
simplifications, generalizations and omissions of detail;
consequently, those skilled in the art will appreciate that the
summary is illustrative only and is NOT intended to be in any way
limiting. Other aspects, inventive features, and advantages of the
devices and/or processes described herein, as defined solely by the
claims, will become apparent in the non-limiting detailed
description set forth herein.
BRIEF DESCRIPTION OF THE FIGURES
[0041] FIG. 1 depicts one aspect of a system that may serve as an
illustrative environment of and/or for subject matter
technologies.
[0042] FIG. 2 depicts a partial view of a system that may serve as
an illustrative environment of and/or for subject matter
technologies.
[0043] FIG. 3 depicts a partial view of a system that may serve as
an illustrative environment of and/or for subject matter
technologies.
[0044] FIG. 4 depicts a diagrammatic view of one aspect of an
exemplary interaction of an immune response component, for example,
an antibody interacting with an epitope displayed by an agent.
[0045] FIG. 5 depicts a diagrammatic view of one aspect of a method
of enhancing an immune response.
[0046] FIG. 6 depicts one aspect of an antigen-antibody interaction
showing the occurrence of mutational changes in a selected epitope
and corresponding changes in a complementary antibody.
[0047] FIG. 7 is an illustration of one aspect of mutational
changes in an epitope displayed by an agent and the corresponding
changes in an immune response component, for example, an
antibody.
[0048] FIG. 8 depicts a high-level logic flowchart of a
process.
[0049] FIG. 9A depicts a high-level logic flowchart depicting
alternate implementations of the high-level logic flowchart of FIG.
8.
[0050] FIG. 9B depicts a high-level logic flowchart depicting
alternate implementations of the high-level logic flowchart of FIG.
8.
[0051] FIG. 10 depicts a high-level logic flowchart depicting
alternate implementations of the high-level logic flowchart of FIG.
8.
[0052] The use of the same symbols in different drawings typically
indicates similar or identical items.
DETAILED DESCRIPTION
[0053] The present application uses formal outline headings for
clarity of presentation. However, it is to be understood that the
outline headings are for presentation purposes, and that different
types of subject matter may be discussed throughout the application
(e.g., device(s)/structure(s) may be described under the
process(es)/operations heading(s) and/or process(es)/operations may
be discussed under structure(s)/process(es) headings). Hence, the
use of the formal outline headings is not intended to be in any way
limiting.
[0054] With reference to the figures, and with reference now to
FIG. 1, depicted is one aspect of a system that may serve as an
illustrative environment of and/or for subject matter technologies,
for example, a computer-based method for designating an immune
response component for modulating an epitope and/or a computable
epitope displayed by an agent. Accordingly, the present application
first describes certain specific exemplary systems of FIG. 1;
thereafter, the present application illustrates certain specific
exemplary structures and processes. Those having skill in the art
will appreciate that the specific structures and processes
described herein are intended as merely illustrative of their more
general counterparts. It will also be appreciated by those of skill
in the art that an epitope-antibody, a computable epitope-antibody
interaction, an immune cell receptor-epitope and/or immune-cell
secretion product-epitope, and/or an antigen-antibody interaction
is an exemplary interaction of an immune response component with an
epitope, a computable epitope, and/or an antigen. Therefore,
although, the exact nature of the interaction may vary, the overall
picture as described herein and/or in other related applications
relates to the interaction of an immune response component
interacting with the epitope, computable epitope, and/or the
antigen. As used herein, the term "epitope" 402 may, if appropriate
to context, be used interchangeably with computable epitope,
antigen, paratope binding site, antigenic determinant, and/or
determinant.
[0055] A. Structure(s) and or System(s)
[0056] Continuing to refer to FIG. 1, depicted is a partial view of
a system that may serve as an illustrative environment of and/or
for subject matter technologies. One or more users 110 may use a
computer system 100 including a computer program 102, for example,
for identifying computable portions of an agent associated with a
disease, disorder, or condition. The computer program 102 may
include one or more instructions, for example, instructions for
identifying an association of at least a computable portion of one
or more agents with at least a part of an immune response 103, for
example, identifying an association based on user defined
parameters. The instructions may be such that, when they are loaded
to a general purpose computer, or microprocessor, programmed to
carry out the instructions they create a new machine, because a
general purpose computer in effect may become a special purpose
computer once it is programmed to perform particular functions
pursuant to instructions from program software. That is, the
instructions of the software program may electrically change the
general purpose computer by creating electrical paths within the
device. These electrical paths, in some implementations, may create
a special purpose machine having circuitry for carrying out the
particular program. The computer program 102 may include
instructions that give rise to circuitry for projecting a pattern
of one or more changes relating to the at least a computable
portion of the one or more agents 104 , for example, mutations,
variations and/or alternate computable portions. The computer
program 102 may include instructions that give rise to circuitry
for selecting one or more immune response components in response to
the projecting 105, for example, including, but not limited to, a
natural and/or a synthetic antibody. The computer program 102 may
accept input, for example, from medical personnel, a researcher, or
wet lab personnel. A user interface may be coupled to provide
access to the computer program 102. In one implementation, the
computer program 102 may access a database 106 for storing
information and transmit an output 107 to the computer system 100.
In one exemplary implementation, a feedback loop is set up between
the computer program 102 and the database 106. The output 107 may
be fed back into the computer program 102 and/or displayed on the
computer system 100. The system may be used as a research tool, as
a tool for furthering treatment or the like. This feedback scheme
may be useful in an iterative process such as described herein and
elsewhere.
[0057] With reference to the figures, and with reference now to
FIG. 2, depicted is a partial view of a system that may serve as an
illustrative environment of and/or for subject matter technologies.
The database 106, data 200, and/or the output 107 may be accessed
by various input mechanisms, for example, mechanisms including but
not limited to, robotic and/or user input via a medical system 204,
robotic and/or user input via manufacturing system 205, or robotic
and/or user input via wet lab system 206. Access to the data 200
may be provided, for example, for further manipulation of the
data.
[0058] With reference to the figures, and with reference now to
FIG. 3, depicted is a partial view of a system that may serve as an
illustrative environment of and/or for subject matter technologies.
In one aspect, a system 300 may include components and/or circuitry
for identifying an association of at least a computable portion of
one or more agents with at least a part of an immune response 304.
The system 300 may include components and/or circuitry for
projecting a pattern of one or more changes relating to the at
least a computable portion of the one or more agents 306. The
system 300 may also include components and/or circuitry for
selecting one or more immune response components in response to the
projecting 308. Those skilled in the art will recognize that some
aspects of the embodiments disclosed herein, in whole or in part,
can be equivalently implemented in standard integrated circuits, as
one or more computer programs running on one or more computers
(e.g., as one or more programs running on one or more computer
systems), as one or more programs running on one or more processors
(e.g., as one or more programs running on one or more
microprocessors), as firmware, or as virtually any combination
thereof, and that designing the circuitry and/or writing the code
for the software and or firmware would be well within the skill of
one of skill in the art in light of this disclosure.
[0059] Continuing to refer to FIG. 3, the system 300 may be-coupled
to a database 314 of an identifiable type 316, for example,
including, but not limited to, a human database, a host database, a
pathogen database, a plant database, an animal database, a
bacterium database, a viral database, a fungal database, a
protoctist database, a prokaryotic database, an eukaryotic
database, a biological database, a genetic database, a genomic
database, a structural database, a SNP database, an immunological
database, an epitopic mapping database, and/or an epidemiological
database. An output 310 may be displayed, for example, in the form
of a protocol 312, for example, including but not limited to a
treatment protocol, a prophylactic protocol, a therapeutic
protocol, an intervention protocol, a dosage protocol, a dosing
pattern (in space, in time and/or in some combination thereof)
protocol, an effective route protocol, and/or a duration of a
dosage protocol. In one aspect the type of output 310 may be
selected by the user.
[0060] In various aspects, the computer system 100, the computer
program 102 and/or the circuitry includes predictive algorithms for
determining the pattern changes in the computable epitope and the
sequence of the computable epitope. In other various aspects, the
computer system 100, the computer program 102 and/or the circuitry
includes predictive algorithms for determining the course of a
disease influenced by the pattern changes in the computable epitope
of the agent.
[0061] In various aspects, the computer system 100, the computer
program 102 and/or the circuitry includes computer-based modeling
software for designing and selecting an immune response component
useful for reducing the ability of the agent to establish itself in
a host and/or to cause a disease, disorder and/or a condition that
requires management.
[0062] In other various aspects, the computer system 100, the
computer program 102 and/or the circuitry includes software for
integrating with other computer-based systems and incorporating
information relevant to selecting an immune response component for
modulating the computable epitopes.
[0063] With reference to the figures, and with reference now to
FIG. 4, depicted is a diagrammatic view of one aspect of an
exemplary interaction of an immune response component, for example,
an antibody 404 interacting with an epitope 402 displayed by an
agent 400, for example, including but not limited to, in
consequence of an interaction involving the agent 400. Those
skilled in the art will appreciate that in some contexts, an
epitope may sometimes be viewed as a type of antigen.
[0064] The term "immune response component," as used herein, may
include, but is not limited to, at least a part of a macrophage, a
neutrophil, a cytotoxic cell, a lymphocyte, a T-lymphocyte, a
killer T-lymphocyte, an immune response modulator, a helper
T-lymphocyte, an antigen receptor, an antigen presenting cell, a
dendritic cell, a cytotoxic T-lymphocyte, a T-8 lymphocyte, a
cluster differentiation (CD) molecule, a CD3 molecule, a CD1
molecule, a B lymphocyte, an antibody, a recombinant antibody, a
genetically engineered antibody, a chimeric antibody, a
monospecific antibody, a bispecific antibody, a multispecific
antibody, a diabody, a chimeric antibody, a humanized antibody, a
human antibody, a heteroantibody, a monoclonal antibody, a
polyclonal antibody, a camelized antibody, a deimmunized antibody,
an anti-idiotypic antibody, an antibody fragment, and/or a
synthetic antibody and/or any component of the immune system that
may bind to an antigen and/or an epitope thereof in a specific
and/or a useful manner.
[0065] The term "agent", as used herein, 400 may include, for
example, but is not limited to, an organism, a virus, a dependent
virus, an associated virus, a bacterium, a yeast, a mold, a fungus,
a protoctist, an archaea, a mycoplasma, a phage, a mycobacterium,
an ureaplasma, a chlamydia, a rickettsia, a nanobacterium, a prion,
an agent responsible for a transmissible spongiform encephalopathy
(TSE), a multicellular parasite, a protein, an infectious protein,
a polypeptide, a polyribonucleotide, a polydeoxyribonucleotide, a
polyglycopeptide, a polysaccharide, a nucleic acid, an infectious
nucleic acid, a polymeric nucleic acid, a metabolic byproduct, a
cellular byproduct, and/or a toxin. The term "agent" 400 may
include, but is not limited to, a putative causative agent of a
disease or disorder, or a cell or component thereof that is deemed,
for example, a target for therapy, a target for neutralization,
and/or or a cell whose apoptosis, phagocytic envelopment, removal,
lysis or functional degradation may prove beneficial to the host.
The term "agent" 400 may also include, but is not limited to, a
byproduct or output of a cell that may be neutralized and/or whose
removal or functional neutralization may prove beneficial to the
host. Furthermore, the term "agent" 400 may include an agent
belonging to the same family or group as the agent of primary
interest, or an agent exhibiting a common and/or a-biological
function relative to the agent of primary interest.
[0066] The term "antibody" 404, as used herein, is used in the
broadest possible sense and may include but is not limited to an
antibody, a recombinant antibody, a genetically engineered
antibody, a chimeric antibody, a monospecific antibody, a
bispecific antibody, a multispecific antibody, a diabody, a
chimeric antibody, a humanized antibody, a human antibody, a
heteroantibody, a monoclonal antibody, a polyclonal antibody, a
camelized antibody, a deimmunized antibody, an anti-idiotypic
antibody, and/or an antibody fragment. The term "antibody" may also
include but is not limited to types of antibodies such as IgA, IgD,
IgE, IgG and/or IgM, and/or the subtypes IgG1, IgG2, IgG3, IgG4,
IgA1 and/or IgA2. The term "antibody" may also include but is not
limited to an antibody fragment such as at least a portion of an
intact antibody 104, for instance, the antigen binding variable
region. Examples of antibody fragments include Fv, Fab, Fab',
F(ab'), F(ab').sub.2, Fv fragment, diabody, linear antibody,
single-chain antibody molecule, multi specific antibody, and/or
other antigen binding sequences of an antibody. Additional
information may be found in U.S. Pat. No. 5,641,870, U.S. Pat. No.
4,816,567, WO 93/11161, Holliger et al., Diabodies: small bivalent
and bispecific antibody fragments, PNAS, 90: 6444-6448 (1993),
Zapata et al., Engineering linear F(ab')2 fragments for efficient
production in Escherichia coli and enhanced antiproliferative
activity, Protein-Eng. 8(10): 1057-1062 (1995), which are
incorporated herein by reference. Antibodies may be generated for
therapeutic purposes by a variety of known techniques, such as, for
example, phage display, and/or transgenic animals and/or
organisms.
[0067] The term "antibody" 404, as used herein, may include
anti-idiotypic antibodies. Anti-idiotypic antibodies may elicit a
stronger immune response compared to the antigen and may be used
for enhancing the immune response. Anti-idiotypic antibodies may be
rapidly selected, for example, by phage display technology.
Additional information may be found in U.S. Patent Application No.
20040143101, to Soltis which is incorporated herein by
reference.
[0068] The term "antibody" 404, as used herein, also may include,
but is not limited to, functional derivatives of a monoclonal
antibody which include antibody molecules or fragments thereof that
have retained a dominant fraction of the antigenic specificity and
the functional activity of the parent molecule.
[0069] The term "heteroantibody," as used herein, may include but
is not limited to, two or more antibodies, antibody fragments,
antibody derivatives, and/or antibodies with at least one
specificity that are linked together. Additional information may be
found in U.S. Pat. No. 6,071,517, which is incorporated herein by
reference.
[0070] The term "chimeric antibody," as used herein, may include,
but is not limited to, antibodies having mouse-variable regions
joined to human-constant regions. In one aspect, "chimeric
antibody" includes antibodies with human framework regions combined
with complementarity-determining regions (CDRs) obtained from an
animal such as a mouse and/or rat; those skilled in the art will
appreciate that CDRs may be obtained from other sources. Additional
information may be found in EPO Publication No 0239400, which is
incorporated herein by reference.
[0071] The term "humanized antibody," as used herein, may include,
but is not limited to, an antibody having one or more human-derived
regions, and/or a chimeric antibody with one or more human-derived
regions, also considered the recipient antibody, combined with CDRs
from a donor mouse and/or rat immunoglobulin. In one aspect, a
humanized antibody may include residues not found in either donor
and/or recipient sequences. A humanized antibody may have single
and/or multiple specificities. Additional information may be found
in U.S. Pat. No. 5,530,101, and U.S. Pat. No. 4,816,567, which are
incorporated herein by reference. Information may also be found in,
Jones et al., Replacing the complementarity-determining regions in
a human antibody with those from a mouse, Nature,
321:522-525(1986); Riechmann et al., Reshaping human antibodies for
therapy, Nature, 332:323-327 (1988); and Verhoeyen et al.,
Reshaping human antibodies: grafting an antilysozyme activity,
Science, 239:1534 (1988), which are all incorporated herein by
reference.
[0072] The term "human antibody," as used herein, may include, but
is not limited to, an antibody with variable and constant regions
derived from human germline immunoglobulin sequences. The term
"human antibody" may include and is not limited to amino acid
residues of non-human origin, encoded by non-human germline, such
as, for example, residues introduced by site-directed mutations,
random mutations, and/or insertions. Methods for producing human
antibodies are known in the art and incorporated herein by
reference. Additional information may be found in U.S. Pat. No.
4,634,666, which is incorporated herein by reference.
[0073] The term "recombinant antibody," as used herein, may include
antibodies formed and/or created by recombinant technology,
including, but not limited to, chimeric, human, humanized,
hetero-antibodies and/or the like.
[0074] The term "epitope" 402, as used herein, may include, but is
not limited to, a sequence of at least 3 amino acids, a sequence of
at least nine nucleotides, an amino acid, a nucleotide, a
carbohydrate, a protein, a lipid, a capsid protein, a coat protein,
a polysaccharide, a sugar, a lipopolysaccharide, a glycolipid, a
glycoprotein, and/or at least a part of a cell. As used herein, the
term "epitope" 402 may, if appropriate to context, be used
interchangeably with antigen, paratope binding site, antigenic
determinant, and/or determinant. As used herein, the term
"determinant" can include an influencing element, determining
element, and/or factor, unless context indicates otherwise. In one
aspect, the term "epitope" 402 includes, but is not limited to, a
peptide-binding site. As used herein, the term "epitope" 402 may
include structural and/or functionally similar sequences found in
the agent 400. The term "epitope" 402 includes, but is not limited
to, similar sequences observed in orthologs, paralogs, homologs,
isofunctional homologs, heterofunctional homologs, heterospecific
homologs, and/or pseudogenes of the agent 400. The epitope 402 may
include any portion of the agent. In one aspect, the epitope 402
may include at least a portion of a gene or gene-expression
product. In another aspect, the epitope may include at least a part
of a non-coding region.
[0075] The term "computable epitope" as used herein, includes, but
is not limited to, an epitope 402 whose likely future mutable forms
may be predicted by using, for example, including, but not limited
to, practicable computer-based predictive methodology and/or
practicable evolutionary methods and/or practicable probabilistic
evolutionary models and/or practicable probabilistic defect models
and/or practicable probabilistic mutation models. For example,
Smith et al. in their article "Mapping the Antigenic and Genetic
Evolution of Influenza Virus" on the history of the antigenic
evolution of the human influenza virus, Science 305, 371 (2004),
which is incorporated herein by reference in its entirety, present
in this paper's Table 1 and the supporting text thereof a set of
patterns of viral coat-protein epitopic evolution which constitutes
a basis for predicting one or more patterns of epitopic evolution
in this particular agent, which is a well-established threat to
human physiological well-being. In one aspect, the computable
epitope may be suggested by, for example, including, but not
limited to, predictive parallel extrapolations with similar
structure, key residues, and/or the presence or absence of known
domains. In another aspect, mathematics, statistical analysis
and/or biological structural modeling tools may provide the
relevant information for designating or identifying the computable
epitope. One specific example of a computable epitope is a
polypeptide associated with the HIV-1 virus, which may be, for
example, seven to ten amino acids long. Knowing any starting state
of such a polypeptide (e.g., how the various amino acids are
sequenced/arranged), and using current computational techniques, it
is practicable to calculate the likely future combinations of the
seven to ten amino acids in the peptide so as to be able to predict
how the epitope will likely appear as evolution/change occurs in
the epitope as biological processes progress. Indeed, many such
evolutionary progressions in the protein sequences of the viral
proteins (e.g., reverse transcriptase and protease) of the several
major strains of HIV-1 virus have been reported in the literature,
and are used for monitoring the clinical progression of disease in
patients. Consequently, in some implementations, technologies
described herein computationally predict how the epitope(s) will
appear in future mutable forms. This predictive knowledge allows
for the designation of at least one immune response component
operable for modulating (e.g., reducing and/or eliminating) at
least one "future version" of some posited presently existing
epitope. As a specific example, one might predict the five or six
mostly likely ways in which at least one epitope of a viral protein
of a current strain of HIV-1 might appear a few months in the
future, and then designate that a person's immune cells be exposed
to the chemical structures of the epitopes of such an essential
protein of such future HIV-1 strains to produce an immune response
ready, waiting, and keyed to such future epitopic variants of the
at least one HIV-1 strain. Once such antibodies or other immune
response components have been produced, amplification or adjuvant
techniques may be utilized to produce usefully-large quantities of
such antibodies or other immune responses at a time earlier than
the elapsing of the three months, and such antibodies administered
to a host, or a vaccine eliciting such antibodies administered to a
host, or cytotoxic responses prepared in the host, and/or a
combination thereof. Then, if the HIV-1 virus does evolve or mutate
in at least one of the five or six computationally predicted ways,
antibodies or other specific immune responses will be present and
waiting to lock onto and negate the HIV-1 virus as it mutates along
the predicted paths, thereby effectively precluding its `mutational
escape` from the initial therapy. Examples listed supra are merely
illustrative of methodology that may be used for designating the
computable epitope and are NOT intended to be in any way
limiting.
[0076] Continuing to refer to FIG. 4, the epitope 402 or parts
thereof may be displayed by the agent 400, may be displayed on the
surface of the agent 400, extend from the surface of the agent 400,
and/or may only be partially accessible by the immune response
component. In one aspect, the epitope 402 may be a linear
determinant. For example, the sequences may be adjacent to each
other. In another aspect, the epitope 402 may be presented
epitopically as a non-linear determinant, for example, including
juxtaposed groups which are non-adjacent ab initio but become
adjacent to each other on folding, editing, splicing or other
assembly. Furthermore, the sequence of the non-linear determinant
may be derived by proteasomal processing of the antigen and/or
other mechanisms (e.g., glycosolization, or the superficial
`decoration` of proteins with sugars) and the sequence
synthetically prepared, for example, as an epitope for presentation
to the immune response component.
[0077] Continuing to refer to FIG. 4, in one aspect, the immune
system launches a humoral response producing antibodies capable of
recognizing and/or binding to the epitope 402, followed by the
subsequent lysis or degradation of the agent 400. Mechanisms by
which the antigen 402 elicits an immune response are known in the
art and such mechanisms are incorporated herein by reference. In
one aspect, the binding of the antibody 404 to the epitope 402 to
form an antigen-antibody complex 405 is characterized as a
lock-and-key fit. In another aspect, the binding affinity of the
antibody for the epitope may vary in time (e.g., in the course of
`affinity maturation`) or with physiological circumstances. In yet
another aspect, the antigen-antibody complex may bind with varying
degrees of reversibility. The binding or the detachment of the
antigen-antibody complex may be manipulated, for example, by
providing a small (possibly solvated) atom, ion, molecule or
compound that promotes the association or disassociation.
[0078] In one aspect, the epitope 402 is capable of evoking an
immune response. The strength and/or type of the immune response
may vary, for example, the epitope 402 may invoke a weak response
and/or a medium response as measured by the strength of the immune
response. It is contemplated that in one instance the epitope 402
selected for targeting may be one that invokes a weak response in
the host; however, it may be selective to the agent 400. In another
example, the epitope 402 selected may invoke a weak response in the
host; however, it may be selected for targeting as it is common to
a number of agents deemed to be targets. The herein described
implementations are merely exemplary and should-be considered
illustrative of like and/or more general implementations within the
ambit of those having skill in the art in light of the teachings
herein.
[0079] With reference to the figures, and with reference now to
FIG. 5, depicted is a diagrammatic view of one aspect of a method
of enhancing an immune response. In one aspect, an effective
treatment therapy towards a disease and/or a disorder may utilize
one or more immune response components designed to recognize one or
more epitopes common to one or more agents. Such common or shared
epitopes may represent an effective target group of epitopes. The
immune response components designed to seek out and neutralize the
common epitopes may be effective against one or more agents.
[0080] In one aspect, the one or more agents may be subtypes of the
agent 400. In this aspect, a set of epitopes may be selected for
targeting an agent. In another aspect, the one or more agents may
be opportunistic agents capable of aiding or exaggerating an
infection formed by the agent 400. In yet another aspect, the one
or more agents may be agents known to establish a foothold in the
host organism prior to or subsequent to an infection or in response
to a host's attenuated immune response.
[0081] With reference now to FIGS. 4 and 5, in one aspect, a shared
epitope 506 is depicted as common to three agents 530, 510 and 520.
In another aspect, a second shared epitope 512 is common to two
agents 530 and 510. In yet another aspect, a third shared epitope
518 is common to two agents 510 and 520. Finding a subset of common
epitopes shared amongst one or more agents may be done by
statistical analysis, for example, by metaprofiling.
[0082] Continuing to refer to FIGS. 4 and 5, in one aspect, one or
more agents 530, 540, and 520 depicted may share a subset of common
epitopes. The selection of epitopes may depend on a number of
criteria. For example, the initial selection may be based on
selection criteria including, but not limited to, the number of
instances of presentation of the epitope 402 by one or more agents,
the number of instances of presentation of the epitope 402 by the
agent 400, the location of the epitope 402, the size of the epitope
402, the nature of the epitope 402, the comparative sequence
identity and/or homology of the epitope 402 with host sequences,
the composition of the epitope 402, and/or putative known or
predicted changes in the epitope 402 sequence. The selection of
epitopes may also depend on, for example, the type of immune
response component desired for treating and/or managing the
disease, disorder, and/or condition.
[0083] In one aspect, the epitope 402 selected has a probable
sequence match with another agent of interest, for example, an
opportunistic agent, or a subsequent or parallel infection caused
by another agent. In another aspect, the epitope 402 selected has a
probable (e.g., low) match with the host self-epitopes, for
example, so as to decrease possible side-effects due to the
production of self or auto-antibodies. In another aspect, the
epitope 402 selected has a probable (e.g., high) match with the
host self-epitopes, for example, so as to decrease unwanted
infected cells. The term "host," as used herein, may include but is
not limited to an individual, a person, a patient, and/or virtually
any organism requiring management of a disease, disorder, and/or
condition. For example, the epitope 402 selected may have a 0-70%
sequence match at the amino acid level with the host or the agent
400, or a 0-100% sequence match with the agent. Those having skill
in the art will recognize that part of that context in relation to
the term "host" is that generally what is desired is a practicably
close sequence match to the agent (e.g., HIV-1 or influenza-A
virus), so that the one or more immune system components in use can
attack it at a practicably-distant sequence match to the host
(e.g., a patient), in order to decrease or render less aggressive
or less likely any attack by the immune system components in use on
the host. However, it is also to be understood that, in some
contexts, the agent will in fact constitute a part of the host
(e.g., when the agent to be eradicated is actually a malfunctioning
part of the host, such as in an auto-immune or neoplastic disease),
in which case that part of the host to be eradicated will be
treated as the "agent," and that part of the host to be left
relatively undisturbed will be treated as the "host." In another
aspect, the epitope 402 selected has a sequence match with the
agent, for example, a high sequence match, or a relatively higher
sequence match with other agents compared to the host, or a 0-100%
sequence match with the agent 400. The term "sequence match," as
used herein, includes sequence matching at the nucleic acid level,
at the protein level, at the polysaccharide level, and/or at the
polypeptide level. In an embodiment, the epitope 402 selected has a
probable (e.g., low) sequence match with the host. In another
embodiment, the epitope 402 selected has a high sequence match with
other agents.
[0084] In molecular biology, the term "percent sequence identity,"
"percent sequence homology" or "percent sequence similarity" are
sometimes used interchangeably. In this application the terms are
also often used interchangeably, unless context dictates
otherwise.
[0085] In another aspect, the epitope 402 selected has a likely
and/or a probable sequence match with other epitopes, for example,
including, but not limited to, the epitope 402 having a structural
sequence match, a functional sequence match, a similar functional
effect, a similar result in an assay and/or a combination.
Structural comparison algorithms and/or 3-dimensional protein
structure data may be used to determine whether two proteins or
presented fragments thereof may have a structural sequence match.
In another example, the epitope 402 may have a functional match
and/or share a similar functional effect with epitopes of interest.
In this example, the epitope 402 may have a lower probable sequence
match but may still exert the same functional effect. In another
example, the epitope 402 and/or other epitopes of interest may have
a lower probable sequence match but may share similar activities,
for example, enzymatic activity and/or receptor binding activity,
e.g., as determined by use of an assay.
[0086] In another aspect, the epitope 402 selected may be an
immunological effective determinant; for example, the epitope 402
may be weakly antigenic, however it may invoke an effective immune
response relating to, for example, the nature and/or the type of
the immune response component it evokes. In another aspect, the
epitope 402 may exert a similar effect on the immune response; for
example, the epitope 402 selected may be part of the antigenic
structure of an agent unrelated to the disease or disorder in
question; however, it may exert a substantially similar effect on
the immune system as measured by, for example, the type, the
nature, and/or the time-interval of the immune response.
[0087] In one aspect, a sequence match with an entity may be
quantified by, for example, calculating the percent identity and/or
percent similarity between epitopes and/or between the epitope 400
and the host. In one aspect, the percent identity between two
sequences may be calculated by determining a number of
substantially similar positions obtained after aligning the
sequences and introducing gaps. For example, in one implementation,
the percent identity between two sequences is treated as equal to
(=) {the number of substantially similar positions/the total number
of positions}.times.100. In this example, the number and length of
gaps introduced to obtain optimal alignment of the sequences are
considered. In another aspect, the percent identity between two
sequences at the nucleic acid level may be determined by using a
publicly available software tool such as BLAST, BLAST-2, ALIGN
and/or DNASTAR software. Similarly, the percent identity between
two sequences at the amino acid level may be calculated by using
publicly available software tools such as, for example,
Peptidecutter, AACompSim, Find Mod, GlycoMod, InterProtScan, DALI
and/or tools listed on the ExPasy Server (Expert Protein Analysis
System) Proteomics Server at http://www.expasy.org/. In one
embodiment, the percent identity at the nucleic acid level and/or
at the amino acid level are determined.
[0088] In one aspect, string-matching algorithms may be used to
identify homologous segments, for example, using FASTA, and BLAST.
In another aspect, sequence alignment based on fast Fourier
transform (FFT) algorithms may be used to rapidly identify
homologous segments. In yet another aspect, iterative searches may
be used to identify and select homologous segments. Searches may be
used not only to identify and select shared epitopes but also to
identify epitopes that have the least homology with human
sequences. Additional information may be found in Katoh et al.,
MAFFT: a novel method for rapid multiple sequence alignment based
on fast Fourier transform, Nucleic Acids Research, 30(14):3059-66
(2002) which is incorported herein by reference.
[0089] A number of large-scale screening techniques may be used to
identify and select the designed antibody, for example, the
antibody designed may be selected by using optical fiber array
devices capable of screening binding molecules. Additional
information may be found in U.S. Patent Application No. 20040132112
to Kimon et al., which is hereby incorporated by reference.
[0090] It will be appreciated by those skilled in the art that the
epitope 402 selected need not be limited to a matching sequence
displayed by the agent 400. In one aspect, a meta-signature and/or
a consensus sequence may be derived based on any number of
criteria. In one aspect, the meta-signature may be derived by
analysis of data from sources such as, for example, antigenic
evolution, genetic evolution, antigenic shift, antigenic drift,
data from crystal structure, probable match with a host, probable
match with other strains, and/or strength of the immunogenic
response desired. The meta-signature may include new sequences
and/or may exclude some sequences. For example, it may include
silent mutations, mismatches, a spacer to bypass a hotspot or a
highly mutagenic site, predicted changes in the sequence, and/or
may include epitopes from multiple agents, thus providing
protection from multiple agents. As another example, the
meta-signature may exclude sequences, such as, for example,
including, but not limited to, mutagenic sequences and/or sequences
with a high percent sequence match to a host sequence.
[0091] In one aspect, the predicted changes in the epitope 402 may
be determined by analysis of past variations observed and/or
predicted in the agent 400.(e.g., FIG. 5). Computational analysis
can be used to determine regions showing sequence variations and/or
hot spots. In one aspect, high-speed serial passaging in silico may
be performed, computationally mimicking the serial passaging that
occurs naturally with a production of a new strain of the agent
400. It will be appreciated by those of skill in the art that the
hot spots need not be identified by examining the epitope 402,
and/or by examining the epitope 402 in context with the agent 400.
Information pertaining to hot spots can also be extrapolated by
performing sequence analysis of other agents and/or domain analysis
of such other agents. For example, in one implementation, the
epitope 402 may be part of a domain shared between multiple agents,
some of which may lack the epitope 402 of interest. Information
pertaining to hot spots identified in the domain of the other
agents may be of practical use in determining the
meta-signature.
[0092] In one aspect, one or more sets and/or subsets of epitopes
may be formed. The nature and type of criteria used to form the
sets and/or subsets will depend, for example, on the nature and
type of the agent 400, the duration of the immune response desired
(e.g., short-term immunity, or long-term immunity), the nature of
the immune response desired (e.g., weak, moderate, or strong),
features of the population to be protected (e.g., presence and/or
currency of varying degrees of prior exposure) and the like. The
sets and/or subsets so formed may accept input either robotically
or from a user (e.g., from a manufacturer of immune response
components, from wet lab, and/or from medical or research
personnel).
[0093] The pattern changes predicted in the epitope 402 may be
supplemented, for example, by other methodology, statistical
analysis, historical data, and/or other extrapolations of the type
utilized by those having skill in the art. The knowledge of these
predicted pattern changes represents an arsenal in the design
and/or selection of the immune response components. The predicted
pattern changes may be used to determine the progression of the
changes in the immune response component required to manage such
changes. Inferring the pattern changes in the epitope 402 and using
the information to modulate the progressing response may help
manage the response more effectively. For example, the pattern
changes may be used to provide a timeline of when the therapy could
be changed, what therapy should constitute the change, or the
duration of the change. As a more specific example, one reason why
Type-1 Human Immunodeficiency Virus (HIV-1) is able to eventually
kill its human hosts is that the virus mutates its antigenic
signature-profile significantly faster than the human immune system
can track and respond to these mutations. In a specific
implementation of the subject matter described herein, a sample of
HIV-1 is taken from a patient at a point in time and computational
biological techniques are used to infer likely mutations of the
antigenic signature-profile of the virus at future times.
Techniques such as cloning are then utilized to synthesize immune
system-activating aspects of the anticipated-future HIV strains,
and thereafter replicative techniques are utilized to rapidly
generate copious amounts of one or more immune system components
(e.g., antibodies) that are keyed to the likely future generation
of the patient's particular strain and sub-strain(s) of HIV-1. Once
prepared, the immune system components are then administered to the
patient and thus are present and waiting for the HIV-1 viral
quasispecies when it mutates into the anticipated new forms and/or
attempts to proliferate these forms. If the HIV-1 viral
quasispecies mutates as anticipated, the preloaded immune response
components successfully negate the mutated quasispecies, thereby
likely greatly reducing the patient's viral load--and crucially
suppressing the likelihood of further mutation, since the virion
population of mutated forms never becomes substantial. In another
implementation, the mutational history of the HIV-1 quasispecies is
closely tracked, and once the actual mutational direction has been
determined, high-speed techniques are utilized to generate immune
system components capable of effective suppression of the mutated
viral quasispecies, significantly more rapidly than the virus is
able to effectively mutate and thus `escape` from the suppressive
therapy.
[0094] In one aspect, the epitope 402 selected for designating the
immune response component may be synthetically made and/or derived
from the agent 400. In one embodiment, the epitope 402 selected is
derived from an agent 400 extracted from an individual desiring
treatment and/or an individual found resistant to that agent. In
one aspect, the epitope 402 selected for designating the immune
response component may include multiple copies of the exact same
epitope and/or multiple copies of different epitopes.
[0095] In one aspect, the meta-signature includes sequences
matching adjacent and/or contiguous sequences. In another aspect,
the meta-signature includes non-adjacent sequences. For example, it
will be appreciated by those of skill in the art that peptide
splicing and/or proteosomal processing of the epitope 402 that
occurs naturally may result in the formation of a new epitope, for
example, a non-linear epitope. In this example, proteosomal
processing may result in the excision of sequences and the
transposing non-contiguous sequences to form the non-linear
epitope. Additional information may be found in Hanada et al.,
Immune recognition of a human renal cancer antigen through
post-translational protein splicing, Nature 427:252 (2004), and
Vigneron et al., An antigenic peptide produced by peptide splicing
in the proteosome, Science 304:587 (2004) hereby incorporated by
reference herein in their entirety.
[0096] Additionally, it will also be appreciated by those of skill
in the art that the meta-signature may include sequences displayed
on two different parts of the agent 400. For example, non-adjacent
sequences may appear adjacent each other when the protein is
folded. In this aspect, the meta-signature may include the
non-adjacent sequences for identifying the meta-signature.
Furthermore, the meta-signature may include non-adjacent sequences
corresponding to a specific conformational state of a protein.
Immune response components designed to bind such sequences may be
specific to the conformational state of the protein. 3-D and/or
crystal structure information may also be used to designate the
meta-signature.
[0097] In one aspect, the meta-signature may include multiple sets
of epitopes targeting a predicted pattern change and/or an observed
pattern change. For example, multiple sets of epitopes may be
designed for vaccination and/or for production of immune response
components.
[0098] Techniques for epitope mapping are known in the art and
herein incorporated by reference. For example, FACS analysis and
ELISA may be used to investigate the binding of antibodies to
synthetic peptides including at least a portion of the epitope.
Epitope-mapping analysis techniques, Scatchard analysis and the
like may be used to predict the ability of the antibody 404 to bind
to the epitope 402 presented on the agent 100, to determine the
binding affinity of the antibody or other immune element 404 to the
epitope 402, and/or to discern a desirable configuration for the
antibody or other immune element 404.
[0099] Continuing to refer to FIG. 5, in one aspect, for example,
the sequences of selected epitopes 506, 512, and/or 518 may be used
to design one or more complementary antibodies or other immune
elements 524, 522, and /or 526, respectively. The sequences of
selected epitopes 506, 512, and/or 518 may be used to form
monoclonal antibodies, for example, by cloning or by using
human-mouse systems.
[0100] The sequences of selected epitopes 506, 512, and 518 may be
amplified using the polymerase chain reaction (PCR) as described in
U.S. Pat. Nos. 4,683,195, 4,683,202, and 4,800,159 to Mullis, et
al. which are incorporated herein in their entirety. In another
aspect, a consensus sequence and/or a meta-signature may be
designed and amplified. The relevant sequence(s) may be inserted in
an expression vector for producing proteins and the expressed
protein(s) subsequently used to produce antibodies specific to the
selected epitopes. In one aspect, the selected epitopes may be
antigenic but may not be directly immunogenic.
[0101] Human antibodies may be made, for example, by using a
human-mouse system such as, for example, the Xenomouse technology
of Abgenix, Inc., (available from Abgenix, Inc. currently having
corporate headquarters in Fremont, Calif. 94555) and/or the HuMAb
Mouse technology of Medarex, Inc., (available from Medarex Inc.
currently having corporate headquarters in Annadale, N.J.). In
these systems, the host mouse immunoglobulin genes are inactivated
and human immunoglobulin genes are inserted in the host. On
stimulation with an antigen, such transgenic mice produce fully
human antibodies. Subsequently, human monoclonal antibodies can be
isolated according to standard hybridoma technology.
[0102] Selection of humanized antibodies with higher binding
affinities from promising murine antibodies may be performed by
using computer modeling software developed by Queen, et al. The
antibodies produced by this method include approximately 90% of the
pertinent human sequences. The structure of the specific antibody
is predicted based on computer modeling and the retaining of key
amino acids predicted to be necessary to retain the shape and,
therefore, the binding specificity of the complementarity
determining regions (CDRs). Thus, key murine amino acids are
substituted into the human antibody framework along with murine
CDRs. The software may then be used to test the binding affinity of
the redesigned antibody with the antigen. Additional information
can be found in U.S. Pat. No. 5,693,762 to Queen, et al., which is
incorporated herein by reference
[0103] The formation of other antibody fragments, such as, for
example, Fv, Fab, F(ab').sub.2 or Fc may be carried out by, for
example, phage antibody generated using the techniques as described
in McCafferty et al., Phage antibodies: filamentous phage
displaying antibody variable domains, Nature 348:552-554 (1990),
and Clackson et al., Making Antibody Fragments Using Phage Display
Libraries, Nature 352:624-628 (1991) and U.S. Pat. No. 5,565,332 to
Hoogenboom, et al., which is incorporated herein by reference.
Surface plasmon resonance techniques, for instance, may be used to
analyze real-time biospecific interactions. Camelized antibodies,
deimmunized antibodies and anti-idiotypic antibodies may be
selected by techniques known in the art, which are herein
incorporated by reference.
[0104] In one aspect, the selection of antibodies for modulating
the immune response may be based on their function. For example,
activating antibodies, blocking antibodies, neutralizing
antibodies, and/or inhibitory antibodies may be used to modulate
the immune response. Such antibodies may perform one or more
functions under the appropriate conditions. In a more specific
example, the antibody 404 may be triggered to undergo a
conformational change by providing a cofactor and/or by changing
the ambient temperature or other ambient conditions, such as
overall osmolality or pH or concentration of a particular compound,
atom or ion. The conformation change may result in a new function
being performed by the antibody 404.
[0105] Techniques for purifying antibodies are known in the art and
are incorporated herein by reference. The purified complementary
antibodies 530, 528, or 532 may then be made available for
therapeutic and/or prophylactic treatment.
[0106] The term "an effective treatment therapy," as used herein,
includes, but is not limited to, the use of immune response
components in combination with other antibodies, antibody
fragments, and/or in combination with other treatments, including,
but not limited to, adjuvants, drugs, vitamins hormones, medicinal
agents, pharmaceutical compositions and/or other therapeutic and/or
prophylactic combinations. In another aspect, the immune response
component may be used in combination, for example, with a modulator
of an immune response and/or a modulator of an antibody. In one
aspect, cocktails of immune response components may be
administered, for example, by injecting or otherwise applying or
inserting by a subcutaneous, nasal, intranasal, intramuscular,
intravenous, intraarterial, intrathecal, intracapsular,
intraorbital, intracardiac, transdermal, subdermal. intradermal,
intraperitoneal, transtracheal, subcuticular, intraarticular,
subcapsular, subarachnoidal, intraspinal, epidural, intrasternal,
infusion, topical, sublingual, and/or enteric route.
[0107] The therapeutic effect of the immune response component may
be produced by one or more modes of action. For example, in one
aspect, the immune response component may produce a therapeutic
effect and/or alleviate the symptoms by targeting specific cells or
other biological entities (e.g., virions) and neutralizing them. In
another aspect, the immune response component may bind to and/or
block receptors present on the agent 400 and/or may directly and/or
indirectly block the binding of molecules, such as, for example,
cytokines, exogenous signals and/or growth factors, to the agent
400. In another aspect, the therapeutic effect of the immune
response component is produced by functioning as signaling
molecules. In this example, the immune response component may
induce cross-linking or other functional association of receptors
with subsequent induction of programmed cell death (apoptosis).
[0108] The immune response component may be engineered to include,
for example, one or more effector molecules, such as, for example,
drugs, small molecules, enzymes, toxins, radionuclides, cytokines,
and/or DNA molecules. In this example, the immune response
component may serve as a vehicle for targeting and binding the
agent 400 and/or delivering the one or more effector molecules. In
one aspect, the immune response component may be engineered to
include the one or more effector molecules without the natural
effector functions of the immune response component.
[0109] In another aspect, one or more immune response components
may be coupled to molecules for promoting immune system components
to eliminate unwanted cells. This technique has been described for
the treatment of tumors, viral-infected cells, fungi, and bacteria
using antibodies. Additional information may be found in U.S. Pat.
No. 4,676,980 to Segal, which is incorporated herein by
reference.
[0110] With reference to the figures, and with reference now to
FIG. 6, depicted is one aspect of an antigen-antibody interaction
showing the occurrence of mutational changes in a selected epitope
and corresponding changes in a complementary antibody. The selected
epitope 506 may undergo mutational changes. Other epitopes 602
and/or 608 may not be selected, for example, as the mutation rate
for these epitopes may be substantially high. These mutations may
be random and, therefore, non-predictable, or they may be
predictable. For example, a mutation may be substantially more
predictable based on the occurrence of hot spots or known
mutational history. The complementary antibody or other immune
response component 624 may bind the selected epitope 506, for
example, with a usefully-high affinity. However, a sequence change
610 depicted in a mutated selected epitope 629 may reduce the
binding affinity of the complementary antibody or other immune
response component 624. A complementary antibody or other immune
response component incorporating the mutation 628 may restore the
binding affinity, for example, to a usefully-high binding affinity.
Similarly, appearance of mutations 610, 611 and 612 may require a
new complementary antibody or other immune response component 626
in order to attain a usefully-high binding affinity. Additionally,
the appearance of mutations 610 and 611 may require a new
complementary antibody or other immune response component 627. The
predictive aspect of the computer system, software and/or circuitry
may be used to make mathematically predictable hypotheses regarding
the variations and the treatment components required. In one
aspect, the complementary antibody or other immune response
component need not have a high binding affinity. For example, the
new antibody or other immune response component 626 may be used to
bind and modulate the agents with mutations 610, 611 and/or
612.
[0111] In another aspect, the antibodies or other immune response
components with higher binding affinities may be selected. Numerous
techniques exist for enhancing the binding affinity of the antibody
or other immune component for the epitope 402. In one aspect, the
binding affinity of the antibody or other immune response
components for the epitope 402 may be enhanced by constructing
phage display libraries from an individual who has been immunized
with the epitope 402 either by happenstance or by immunization. The
generation and selection of higher affinity antibodies may also be
improved, for example, by mimicking somatic hypermutagenesis,
complementarity-determining region (CDR) walking mutagenesis,
antibody chain shuffling, and/or technologies such as Xenomax
technology (available from Abgenix, Inc. currently having corporate
headquarters in Fremont, Calif. 94555). In one example, antibodies
including introduced mutations may be displayed on the surface of
filamentous bacteriophage. Processes mimicking the primary and/or
secondary immune response may then be used to select the desired
antibodies, for example, antibodies displaying a higher binding
affinity for the antigen, and/or by evaluating the kinetics of
dissociation. For additional information see, Low et al., Mimicking
Somatic Hypermutation: Affinity Maturation Of Antibodies Displayed
On Bacteriophage Using A Bacterial Mutator Strain, J. Mol. Biol.
260:359-368 (1996); Hawkins et al. Selection Of Phage Antibodies By
Binding Affinity. Mimicking Affinity Maturation, J. Mol. Biol.
226:889-896 (1992), which are incorporated herein by reference.
[0112] In another example, the generation and/or selection of
higher affinity antibodies may be carried out by CDR walking
mutagenesis, which mimics the tertiary immune selection process.
For example, saturation mutagenesis of the CDRs of the antibody 404
may be used to generate one or more libraries of antibody fragments
which are displayed on the surface of filamentous bacteriophage
followed by the subsequent selection of the relevant antibody using
immobilized antigen. Sequential and parallel optimization
strategies may be used to then select the higher affinity antibody.
For additional information see Yang et al., CDR Walking Mutagenesis
For The Affinity Maturation Of A Potent Human Anti-HIV-1 Antibody
Into The Picomolar Range, J. Mol. Biol 254(3):392-403 (1995), which
is incorporated herein by reference in its entirety.
[0113] In yet another example, site-directed mutagenesis may be
used to generate and select higher affinity antibodies, for
example, by parsimonious mutagenesis. In this example, a
computer-based method is used to identify and screen amino acid
residues included in the one or more CDRs of a variable region of
an antibody 104 involved in an antigen-antibody binding.
Additionally, in some implementations, the number of codons
introduced is such that about 50% of the codons in the degenerate
position are wild-type. In another example, antibody
chain-shuffling may be used to generate and select higher affinity
antibodies. These techniques are known in the art and are herein
incorporated by reference.
[0114] The dosage of the immune response component may vary and in
one aspect may depend, for example, on the duration of the
treatment, body mass, severity of the disease, and/or age.
Compositions including immune response components may be delivered
to an individual for prophylactic and/or therapeutic treatments. In
one aspect, an individual having a disease and/or condition is
administered a treatment dose to alleviate and/or at least
partially cure the condition expressed by the symptoms. In this
example, a therapeutically-effective dose is administered to the
patient.
[0115] In another aspect, a person's resistance to disease
conditions may be enhanced by providing a prophylactically measured
dose of the antibody 404. A prophylactic dose may be provided to,
for example, including, but not limited to, a person genetically
predisposed to a disease and/or condition, a person being present
in a region where a particular disease is prevalent, and/or a
person wishing to enhance that person's immune response.
[0116] Optimization of the physico-chemical properties of the
immune response component may be improved, for example, by
computer-based screening methods. Properties affecting antibody
therapeutics may also be improved, such as, for example, stability,
antigen binding affinity, and/or solubility. Additional information
may be found in U.S. Patent Application No. 20040110226 to Lazar,
which is incorporated herein by reference.
[0117] With reference to the figures, and with reference now to
FIGS. 4, 5, and 6, depicted is one aspect of the antigen-antibody
interaction showing the occurrence of mutational changes in the
selected epitope 506 and corresponding changes in the complementary
antibody or other immune response component 524. Such mutational
changes in the selected epitope 506, for example, may be minor or
major in nature. These minor and/or major antigenic variations may
render an existing treatment less effective. Thus an effective
treatment therapy of a disease or disorder may include treating the
disease or disorder with one or more antibodies designed to
anticipate one or more predictable antigenic variations, for
example, including, but not limited to, of one or more agents or
one or more related agents, and/or shared with at least two agents.
Furthermore, predicting the course of the minor and/or major
antigenic variations of the agent 400 and/or the related agents
would also be beneficial in designing or selecting these one or
more anticipatory antibodies. Additionally, in some implementations
the inclusion of information from SNP databases is helpful in
designing antibodies for binding the selected epitope 506.
[0118] Minor changes in the epitope 402 which do not always lead to
the formation of a new subtype may be caused, for example, by point
mutations in the selected epitope 506. In one aspect, the
occurrence of point mutations may be localized, for example, to
hotspots of the selected epitope 506. The frequency and/or
occurrence of such hotspots may be predicted by the computer-based
method. Additionally, the method provides for access to databases
including, for example, historical compilations of the antigenic
variations of the agent 400 and/or of the selected epitope 506, for
example, from previous endemics and/or pandemics or the natural
evolutionary history of the disease. Such information may be part
of an epitope profile for charting the progression of the immune
response. For example, including, but not limited to, a point
mutation in the glutamic acid residue at position 92 of the NS1
protein of the influenza-A virus has been shown to dramatically
down-regulate activation of host cytokines. Such information may be
useful in designating the meta-signature.
[0119] Continuing to refer to FIGS. 4, 5, and 6, depicted is that a
mutation 610 in the selected epitope 506 results in a mutated
epitope 629. The term "the selected epitope 506" as typically used
herein, often constitutes a type of the more general term of
"presented epitope," unless context indicates otherwise. The
generation of the mutated epitope 629 may reduce the binding of the
immune response component, for example, the antibody 624. In one
aspect, binding could be enhanced by generating a new antibody 628
corresponding to the mutated epitope 610. The frequency of minor
antigenic variations may be predicted by examining known and/or
predicted mutational hot spots. For example, additional mutations
611 and/or 612 may be predicted by the computer-based method, and
corresponding antibodies 626 and/or 627, respectively, may be
designed to account for such antigenic variations in the mutated
epitopes 630 and/or 631, respectively. In one aspect, an effective
treatment therapy may incorporate this knowledge in the course of
providing an effective humoral response towards the agent 400. For
example, a cocktail of immune response components may include the
antibodies 624, 628, 626, and/or 627 for binding to the selected
epitope 506 and/or its predicted mutated versions. In one aspect,
the cocktail of one or more antibodies or other immune response
components may be supplemented by additional chemicals, drugs,
and/or growth factors. In another aspect, the effective treatment
therapy may include varying doses of immune response components,
for example, a substantially larger or more prolonged or earlier-
or later-administered dosage of 626 relative to 624, 628, and/or
627.
[0120] Referring now to FIG. 7, for example, one or more new
epitopes 700 and/or 704 may appear on the surface of the agent 400.
In one aspect, major changes may occur in the antigenic variants
present on the surface of the agent 400, resulting in the formation
of a new subtype or sub-strain. The appearance of new epitopes
observed, for example, may occur as a result of antigenic shifts,
reassortment, reshuffling, rearrangement of segments, and/or
swapping of segments and generally marks the appearance of a new
virulent and/or pathogenic (sub-)strain of the agent 400. In one
instance, the prediction of the new epitopes may mark the emergence
of a new (sub-)strain, a new subtype, and/or the reemergence of an
older (sub-)strain. In this instance, natural and/or artificial
immune response in an individual alone may not provide adequate
protection. Immune protection and/or humoral protection may be
supplemented with, for example, drugs, chemicals or small molecules
capable of enhancing, supplanting, supplementing or favorably
interacting with the effects of the pertinent immune response
components.
[0121] Generally, when major epitopic and/or antigenic changes do
occur, a larger section of the impacted population succumbs to the
infection, sometimes leading to an epidemic and/or pandemic. This
problem may be alleviated in part, for example, by predicting the
appearance of new (sub-)strains and/or subtypes as a result of the
appearance of new epitopes and/or the disappearance of existing
epitopes. In one aspect, for example, including, but not limited
to, the prediction of the new epitopes, attention may be directed
towards a subset of genes, for example, important for the overall
Darwinian fitness and/or replicative ability and/or infectivity of
the agent 400. For example, examining the appearance of new
subtypes of influenza virus type A shows that the antigenic
variations occur for the most part as a result of mutations in the
neuraminidase and/or hemagglutinin genes.
[0122] In another aspect, the selected epitope 506 may steer clear
of highly variable regions and focus instead on areas having lower
probability of mutations. Thus epitopes selected may circumvent hot
spots of antigenic variations and target other specific regions of
the agent 400, such as, for example, the receptor-binding site(s)
on the surface of the agent 400. In another example, the selected
epitope 506 may not be readily accessible to the immune response
component, for example, the receptor-binding site may be buried
deep in a `pocket` of a large protein and may be surrounded by
readily accessible sequences exhibiting higher level(s) of
antigenic variation(s). In this example, one possibility may
include providing small antibody fragments that penetrate the
receptor-binding site and/or prevent the agent 400 from binding to
its target. In another example, a drug and/or chemical may be used
to modify and/or enhance the accessibility of the receptor-binding
site. In yet another example, a chemical with a tag may be used to
bind to the receptor and the tag then used for binding the immune
response component.
[0123] In another aspect, the immune response component may be
designed so as to circumvent the shape changes in the epitope 402
and provide sufficiently effective binding to the epitope 402, even
following mutational change therein. In this example, the antibody
or other immune response component designed may include
accommodations in its design arising from the prediction of hot
spots and/or the mutational changes in the epitope 402.
[0124] In one aspect, the size of the immune response component may
be manipulated. An immune response component, for example, the
antibody 404, may be designed to include the practicably minimal
binding site required to bind the epitope 402. In another example,
the immune response component may be designed for binding to the
smallest effective determinant.
[0125] In one aspect, an effective treatment therapy towards a
disease and/or disorder may include one or more immune response
components designed to anticipate and/or treat antigenic drift(s)
and/or antigenic shift(s) predicted for multiple agents. The agents
need not be related to each other; for example, the therapy might
be designed for an individual suffering simultaneously from
multiple diseases.
[0126] B. Operation(s) and/or Process(es)
[0127] Following are a series of flowcharts depicting
implementations of processes. For ease of understanding, the
flowcharts are organized such that the initial flowcharts present
implementations via an overall "big picture" or "top-level"
viewpoint and thereafter the subsequent flowcharts present
alternate implementations and/or expansions of the "big picture"
flowcharts as either sub-steps or additional steps building on one
or more earlier-presented flowcharts. Those having skill in the art
will appreciate that the style of presentation utilized herein
(e.g., beginning with a presentation of a flowchart(s) presenting
an overall view and thereafter providing additions to and/or
further details in subsequent flowcharts) generally allows for a
more rapid and reliable understanding of the various process
implementations.
[0128] With reference now to FIG. 8, depicted is a high-level logic
flowchart of a process. Method step 800 shows the start of the
process. Method step 802 depicts identifying an association of at
least a computable portion of one or more agents with at least a
part of an immune response. The computable portion may, for
example, may include, but is not limited to, at least a portion of
an agent requiring management. The computable portion may also
include, at least 3 amino acids, a sequence of at least nine
nucleotides, at least a part of at least one of an amino acid, a
nucleotide, a carbohydrate, a protein, a lipid, a capsid protein, a
coat protein, a polysaccharide, a lipopolysaccharide, a glycolipid,
a glycoprotein, and/or at least a part of a cell or a biological
entity ( e.g., a virus particle). It will be appreciated by those
of skill in the art that the term "amino acid" may include, but is
not limited to, complete and/or partial amino acids, amino acid
residues, amino acid moieties, and/or components thereof. It will
be appreciated by those of skill in the art that the term
"nucleotide" may include, but is not limited to, complete and/or
partial nucleotides (including artificial and/or synthetic
nucleotides and/or nucleotide-mimetics), nucleotide residues,
nucleotide moieties, and/or components thereof. Method step 840
depicts projecting a pattern of one or more changes relating to the
at least a computable portion of the one or more agents. Method
step 870 depicts selecting one or more immune response components
in response to the projecting. Method step 890 shows the
culmination of the process. It will also be appreciated by those
skilled in the art that method steps 800, 802, 840, 870, and/or 890
may include accepting input related to, for example, the agent,
and/or the one or more computable epitopes. Examples of criteria
related to the agent and/or the computable epitopes may include,
but is not limited to, size of the computable epitope, type of the
computable epitope, nature of the disease, nature of disorder,
nature of condition requiring management, and/or a sensitivity of
the group requiring management. Portions of the disclosure herein
(e.g., flowcharts and/or supporting descriptions and/or claims)
refer to "computable portion(s)." Such portions can be modified to
refer to and teach computable epitope(s), epitope(s), and/or
computable antigen(s), as appropriate, especially in light of the
teachings of the as-filed claims. Such modifications of the
portions are within the ambit of those skilled in the art, and
hence are not expressly set forth herein for sake of clarity.
Furthermore, those skilled in the art will appreciate that, in
general, computable portions, computable epitopes, antigens, and/or
computable antigens may be indicative of a part, a section, and/or
a whole and may also be illustrative of a predicted, original, or
mutable sequence (e.g., a sequence including an amino acid, a
nucleotide and/or a sugar) unless context dictates otherwise.
[0129] With reference now to FIG. 9, depicted is a high-level logic
flowchart depicting alternate implementations of the high-level
logic flowchart of FIG. 8. Illustrated is that in various alternate
implementations, method step 870 may include at least one of
substeps 906, 907, 908, 909, 910, and/or 911. Method step 906
depicts selecting at least a part of one or more of a macrophage, a
neutrophil, a cytotoxic cell, a lymphocyte, a T-lymphocyte, a
killer T-lymphocyte, an immune response modulator, a helper
T-lymphocyte, an antigen receptor, an antigen-presenting cell, a
dendritic cell, a cytotoxic T-lymphocyte, a T-8 lymphocyte, a
cluster differentiation (CD) molecule, a CD3 molecule, and/or a CD1
molecule. Method step 907 depicts selecting one or more modulators
of at least a part of at least one of a macrophage, a neutrophil, a
cytotoxic cell, a lymphocyte, a T-lymphocyte, a killer
T-lymphocyte, an immune response modulator, a helper T-lymphocyte,
an antigen receptor, an antigen-presenting cell, a dendritic cell,
a cytotoxic T-lymphocyte, a T-8 lymphocyte, a cluster
differentiation (CD) molecule, a CD3 molecule, and/or a CD1
molecule. Method step 908 depicts selecting at least a part of at
least one B lymphocyte. Method step 909 depicts selecting one or
more of modulators of at least a part of at least one B-lymphocyte.
Method step 910 depicts selecting at least a part of one or more of
an antibody, a recombinant antibody, a genetically engineered
antibody, a chimeric antibody, a monospecific antibody, a
bispecific antibody, a multispecific antibody, a diabody, a
chimeric antibody, a humanized antibody, a human antibody, a
heteroantibody, a monoclonal antibody, a polyclonal antibody, a
camelized antibody, a deimmunized antibody, an anti-idiotypic
antibody, and/or an antibody fragment. Method step 911 depicts
selecting one or more of a modulator of at least a part of at least
one of an antibody, a recombinant antibody, a genetically
engineered antibody, a chimeric antibody, a monospecific antibody,
a bispecific antibody, a multispecific antibody, a diabody, a
chimeric antibody, a humanized antibody, a human antibody, a
heteroantibody, a monoclonal antibody, a polyclonal antibody, a
camelized antibody, a deimmunized antibody, an anti-idiotypic
antibody, and/or an antibody fragment.
[0130] With reference now to FIG. 10, depicted is a high-level
logic flowchart depicting alternate implementations of the
high-level logic flowchart of FIG. 8. Shown is that in various
alternate implementations, method step 802 may include method step
1002. Method step 1002 depicts identifying an association of at
least a computable portion of at least one of an organism, a virus,
a dependent virus, an associated virus, a bacterium, a yeast, a
mold, a fungus, a protoctist, an archaea, a mycoplasma, a phage, a
mycobacterium, an ureaplasma, a chlamydia, a rickettsia, a
nanobacterium, a prion, an agent responsible for transmissible
spongiform encephelopathy (TSE), a multicellular parasite, a
protein, an infectious protein, a polypeptide, a
polyribonucleotide, a polydeoxyribonucleotide, a polyglycopeptide,
a polysaccharide, a nucleic acid, an infectious nucleic acid, a
polymeric nucleic acid, a metabolic byproduct, a cellular
byproduct, and/or a toxin.
[0131] C. Variation(s), and/or Implementation(s)
[0132] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect, the immune response components
may be formulated to cross the blood-brain barrier which is known
to exclude mostly hydrophilic compounds, as well as to discriminate
against transport of high molecular weight ones. For example, an
antibody fragment may be encased in a lipid vesicle. In another
example, the antibody or a portion of the antibody may be tagged
onto a carrier protein or molecule. In another example, an antibody
or other immune response component may be split into one or more
complementary fragments, each fragment encased by a lipid vesicle,
and each fragment functional only on binding its complementary
fragment. Once the blood-brain barrier has been crossed, the lipid
vesicle may be dissolved to release the antibody fragments which
reunite with their complementary counterparts and may form a fully
functional antibody or other immune response component. Other
modifications of the subject matter herein will be appreciated by
one of skill in the art in light of the teachings herein.
[0133] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect, the immune response components
may be made in large format. The method lends itself to both small
format or personalized care applications and large-scale or large
format applications. Other modifications of the subject matter
herein will be appreciated by one of skill in the art in light of
the teachings herein.
[0134] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect, the method may be used to
designate immune response components for any diseases or disorders.
The application of this method is not limited to diseases where
antigenic shift or drift keeps the immune system "guessing" or
causing it to be effectively slow-to-respond. Although influenza-A
or HIV-1 are among the likely viral-disease-agent candidates for
application of this method, treatment of other diseases, disorders
and/or conditions will likely benefit from this methodology. Other
modifications of the subject matter herein will be appreciated by
one of skill in the art in light of the teachings herein.
[0135] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect, real-time evaluation may be
provided of the antigenic changes by including a portable PCR
machine which samples the environment for (sub-)stains of
infectious pathogens locally present. The information may be sent
remotely to another location or to a portable
material-administering device, for example, a drip-patch device
with a remote sensor, utilized by the potentially-affected person,
resulting in the activation of the necessary immune response
components and thereby providing adequate protection if-and-when
the pathogen may become present in the person's location. As the
evaluation possibly changes in time, the portable administering
device may be controlled to change the dosage or type of immune
response component delivered. Such a portable administering device
operably coupled to a portable PCR machine or a functionally
similar system for polypeptides and/or polysaccharides has a wide
variety of applications, for example, including, but not limited
to, when medical personnel visit an area in which one or more
diseases may be endemic, and/or when military personnel visit
territory in which unknown pathogens may be present. Other
modifications of the subject matter herein will be appreciated by
one of skill in the art in light of the teachings herein.
[0136] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect, an individual may use an
administering device including the immune response components
preprogrammed to provide the user the necessary immune
response-mediated protection over an interval period of time,
and/or to anticipate pattern changes in the epitopes of the agent
100. Other modifications of the subject matter herein will be
appreciated by one of skill in the art in light of the teachings
herein.
[0137] Those having skill in the art will recognize that the
present application teaches modifications of the devices,
structures, and/or processes within the spirit of the teaching
herein. For example, in one aspect, RNA blockers, and/or
single-stranded RNAI technology may be used to down-regulate genes
or components of the immune system in conjunction with the method.
Other modifications of the subject matter herein will be
appreciated by one of skill in the art in light of the teachings
herein.
[0138] Those skilled in the art will appreciate that the foregoing
specific exemplary processes and/or devices and/or technologies are
representative of more general processes and/or devices and/or
technologies taught elsewhere herein, such as in the claims filed
herewith and/or elsewhere in the present application.
[0139] Those having skill in the art will recognize that the state
of the art has progressed to the point where there is little
distinction left between hardware and software implementations of
aspects of systems; the use of hardware or software is generally
(but not always, in that in certain contexts the choice between
hardware and software can become significant) a design choice
representing cost vs. efficiency vs. operational convenience
tradeoffs. Those having skill in the art will appreciate that there
are various vehicles by which processes and/or systems and/or other
technologies described herein can be effected (e.g., hardware,
software, and/or firmware), and that the preferred vehicle will
vary with the context in which the processes and/or systems and/or
other. technologies are deployed. For example, if an implementer
determines that speed and accuracy are paramount, the implementer
may opt for a mainly hardware and/or firmware vehicle;
alternatively, if flexibility is paramount, the implementer may opt
for a mainly software implementation; or, yet again alternatively,
the implementer may opt for some combination of hardware, software,
and/or firmware. Hence, there are several possible vehicles by
which the processes and/or devices and/or other technologies
described herein may be effected, none of which is inherently and
universally superior to the other, in that any vehicle to be
utilized is a choice dependent upon the context in which the
vehicle will be deployed and the specific concerns (e.g., speed,
flexibility, or predictability) of the implementer, any of which
may vary substantially.
[0140] The foregoing detailed description has set forth various
embodiments of the devices and/or processes via the use of block
diagrams, flowcharts, and/or examples. Insofar as such block
diagrams, flowcharts, and/or examples contain one or more functions
and/or operations, it will be understood by those within the art
that each function and/or operation within such block diagrams,
flowcharts, or examples can be implemented, individually and/or
collectively, by a wide range of hardware, software, firmware, or
virtually any combination thereof. In one embodiment, several
portions of the subject matter described herein may be implemented
via Application Specific Integrated Circuits (ASICs), Field
Programmable Gate Arrays (FPGAs), digital signal processors (DSPs),
other integrated formats, or other extensively-integrated formats.
However, those skilled in the art will recognize that some aspects
of the embodiments disclosed herein, in whole or in part, can be
equivalently implemented in standard integrated circuits, as one or
more computer programs running on one or more computers (e.g., as
one or more programs running on one or more computer systems), as
one or more programs running on one or more processors (e.g., as
one or more programs running on one or more microprocessors), as
firmware, or as virtually any combination thereof, and that
designing the circuitry and/or writing the code for the software
and or firmware would be well within the skill of one of skill in
the art in light of this disclosure. In addition, those skilled in
the art will appreciate that the mechanisms of the subject matter
described herein are capable of being distributed as a program
product in a variety of forms, and that an illustrative embodiment
of the subject matter subject matter described herein applies
equally regardless of the particular type of signal-bearing media
used to actually carry out the distribution. Examples of a
signal-bearing media include, but are not limited to, the
following: recordable type media such as floppy disks, hard disk
drives, DVD/CD ROMs, digital tape, and computer memory devices of
various types; and data transmission type-media such as digital and
analog communication links using TDM or IP-based communication
links (e.g., packetized data links).
[0141] In a general sense, those skilled in the art will recognize
that the various aspects described herein which can be implemented,
individually and/or collectively, by a wide range of hardware,
software, firmware, or any combination thereof can be viewed as
being composed of various types of "electrical circuitry."
Consequently, as used herein "electrical circuitry" includes, but
is not limited to, electrical circuitry having at least one
discrete electrical circuit, electrical circuitry having at least
one integrated circuit, electrical circuitry having at least one
application-specific integrated circuit, electrical circuitry
forming a general-purpose computing device configured by a computer
program (e.g., a general-purpose computer configured by a computer
program which at least partially carries out processes and/or
devices described herein, or a microprocessor configured by a
computer program which at least partially carries out processes
and/or devices described herein), electrical circuitry forming a
memory device (e.g., forms of random access memory), and/or
electrical circuitry forming a communications device (e.g., a
modem, communications switch, or optical-electrical equipment).
[0142] Those skilled in the art will recognize that it is common
within the art to describe devices and/or processes in the fashion
set forth herein, and thereafter use standard engineering practices
to integrate such described devices and/or processes into
data-processing systems. That is, at least a portion of the devices
and/or processes described herein can be integrated into a
data-processing system via a reasonable amount of experimentation.
Those having skill in the art will recognize that a typical
data-processing system generally includes one or more of a system
unit housing, a display device, a video display device, a memory
such as volatile and/or non-volatile memory, processors such as
microprocessors and digital signal processors, computational
entities such as operating systems, drivers, user interfaces (e.g.,
graphical), and applications programs, one or more interaction
devices, such as a touch pad or screen, and/or control systems
including feedback loops and control motors (e.g., feedback for
sensing position and/or velocity; control motors for moving and/or
adjusting components such as valves and/or quantities). A typical
data processing system may be implemented utilizing any suitable
commercially available components, such as those typically found in
digital computing/communication and/or network
computing/communication systems.
[0143] All of the referenced U.S. patents, U.S. patent application
publications, U.S. patent applications, foreign patents, foreign
patent applications, and/or non-patent publications referred to in
this specification and/or listed in any Application Data Sheet, are
incorporated herein by reference, in their entireties.
[0144] The herein-described aspects depict different components
contained within, or connected with, different other components. It
is to be understood that such depicted architectures are merely
exemplary, and that in fact many other architectures can be
implemented which achieve the same functionality. In a conceptual
sense, any arrangement of components to achieve the same
functionality is effectively "associated" such that the desired
functionality is achieved. Hence, any two components herein
combined to achieve a particular functionality can be seen as
"associated with" each other such that the desired functionality is
achieved, irrespective of architectures or intermedial components.
Likewise, any two components so associated can also be viewed as
being "operably connected", or "operably coupled", to each other to
achieve the desired functionality, and any two components capable
of being so associated can also be viewed as being "operably
couplable", to each other to achieve the desired functionality.
Specific examples of operably couplable include but are not limited
to physically mateable and/or physically interacting components
and/or wirelessly interactable and/or wirelessly interacting
components.
[0145] While particular aspects of the present subject matter
described herein have been shown and described, it will be apparent
to those skilled in the art that, based upon the teachings herein,
changes and modifications may be made without departing from this
subject matter described herein and its broader aspects and,
therefore, the appended claims are to encompass within their scope
all such changes and modifications as are within the true spirit
and scope of this subject matter described herein. Furthermore, it
is to be understood that the invention is solely defined by the
appended claims. It will be understood by those within the art
that, in general, terms used herein, and especially in the appended
claims (e.g., bodies of the appended claims) are generally intended
as "open" terms (e.g., the term "including" should be interpreted
as "including but not limited to," the term "having" should be
interpreted as "having at least," the term "includes" should be
interpreted as "includes but is not limited to," etc.). It will be
further understood by those within the art that if a specific
number of an introduced claim recitation is intended, such an
intent will be explicitly recited in the claim, and in the absence
of such recitation no such intent is present. For example, as an
aid to understanding, the following appended claims may contain
usage of the introductory phrases "at least one" and "one or more"
to introduce claim recitations. However, the use of such phrases
should not be construed to imply that the introduction of a claim
recitation by the indefinite articles "a" or "an" limits any
particular claim containing such introduced claim recitation to
inventions containing only one such recitation, even when the same
claim includes the introductory phrases "one or more" or "at least
one" and indefinite articles such as "a" or "an" (e.g., "a" and/or
"an" should typically be interpreted to mean "at least one" or "one
or more"); the same holds true for the use of definite articles
used to introduce claim recitations. In addition, even if a
specific number of an introduced claim recitation is explicitly
recited, those skilled in the art will recognize that such
recitation should typically be interpreted to mean at least the
recited number (e.g., the bare recitation of "two recitations,"
without other modifiers, typically means at least two recitations,
or two or more recitations). Furthermore, in those instances where
a convention analogous to "at least one of A, B, and C, etc." is
used, in general such a construction is intended in the sense one
having skill in the art would understand the convention (e.g., "a
system having at least one of A, B, and C" would include but not be
limited to systems that have A alone, B alone, C alone, A and B
together, A and C together, B and C together, and/or A, B, and C
together, etc.). In those instances where a convention analogous to
"at least one of A, B, or C, etc." is used, in general such a
construction is intended in the sense one having skill in the art
would understand the convention (e.g., "a system having at least
one of A, B, or C" would include but not be limited to systems that
have A alone, B alone, C alone, A and B together, A and C together,
B and C together, and/or A, B, and C together, etc.).
* * * * *
References